Assessing the Efficacy and Safety of Brolucizumab Versus... | NCT03802630

NCT03802630

ID	Type	Description	Link
2018-001842-33	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Brolucizumab 6 mg	Experimental	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)	Drug: Brolucizumab 6 mg Other: Sham injection
Aflibercept 2 mg	Active Comparator	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)	Drug: Aflibercept 2 mg Other: Sham injection

Name	Type	Description	Arm Group Labels	Other Names
Brolucizumab 6 mg	Drug	Solution for injection (intravitreal use)	Brolucizumab 6 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 24	BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters. Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning. Missing and censored BCVA values were imputed by Last observation carried forward (LOCF) as the primary approach. Observed values from both scheduled and unscheduled post-baseline visits were used for the LOCF imputation. For subjects with no post-baseline BCVA value, the baseline value was carried forward.	Baseline, Week 24

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in BCVA Averaged Over Week 40 to Week 52	An average BCVA over week 40 to week 52 was calculated. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters. Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study.
Patients with visual impairment due to ME secondary to BRVO diagnosed < 6 months prior to screening.
BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.

Exclusion criteria

Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than BRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Hemiretinal vein occlusion should be excluded.
Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline
Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract)
Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline
Previous use of intraocular or periocular steroids in study eye at any time prior to baseline
Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline
Intraocular surgery in the study eye during the 3-month period prior to baseline
Vitreoretinal surgery in the study eye at any time prior to baseline
Aphakia with the absence of posterior capsule in the study eye

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Phoenix	Arizona	85020	United States
Novartis Investigative Site

Label	URL
Results for CRTH258C2301 from the Novartis Clinical Trials Website	View source
A Plain Language Trial Summary is available on novctrd.com	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
FG001	Aflibercept 2 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 8, 2020	Jul 1, 2022

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00065.4± 11.05 BG00165.0± 10.92 BG00265.2± 10.97

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000117 BG001125 BG002

Race/Ethnicity, Customized

Percentages of race categories can add up to more than 100%, as subjects can have multiple entries of race if applicable.

Number

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG000154 BG001153

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 24

BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.

Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.

Missing and censored BCVA values were imputed by Last observation carried forward (LOCF) as the primary approach. Observed values from both scheduled and unscheduled post-baseline visits were used for the LOCF imputation. For subjects with no post-baseline BCVA value, the baseline value was carried forward.

Full Analysis Set (FAS) included all randomized subjects who received at least one Intravitreal injection of the study treatment.

Posted

Least Squares Mean

Standard Error

Letters read

Baseline, Week 24

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants	OG000226 OG001224

Title

Denominators

Categories

Title	Measurements
	OG00013.1± 0.71 OG00115.0± 0.71

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANOVA		0.018		Least Square Mean Difference	-1.9	Standard Error of the Mean	1.01	2-Sided	95	-3.9	0.1					Non-Inferiority	Non-inferiority was considered established if the lower limit of the corresponding 95% CI for the estimated between group difference (brolucizumab vs. aflibercept) on change from baseline in BCVA at Week 24 is greater than -4 letters.

Secondary

Change From Baseline in BCVA Averaged Over Week 40 to Week 52

An average BCVA over week 40 to week 52 was calculated. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.

Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment.

The number analyzed per row is the number of subjects from the FAS who had a valid assessment for both baseline and the corresponding post baseline period.

Posted

Mean

Standard Deviation

Letters read

Baseline, Week 40 to Week 52

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units

Secondary

Change From Baseline in BCVA Averaged Over Week 64 to Week 76

An average BCVA over week 64 to week 76 was calculated. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.

Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment.

The number analyzed per row is the number of subjects from the FAS who had a valid assessment for both baseline and the corresponding post baseline period.

Posted

Mean

Standard Deviation

Letters read

Baseline, Week 64 to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units

Secondary

Change From Baseline in BCVA by Visit up to Week 76

BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.

Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment.

The number analyzed per row is the number of subjects from the FAS who had a valid assessment for both baseline and the corresponding post baseline visit.

Posted

Mean

Standard Deviation

Letters read

Baseline and every 4 weeks from baseline up to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts

Secondary

Proportion of Participants With a Gain ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline

The summary by visit was conducted based on the BCVA observed from each of the corresponding visits.

BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.

Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.

Every 5 letters represents 1 line of vision on the reading chart.

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment. The number analyzed per row is the number of subjects from the FAS who had a valid assessment for both baseline and the corresponding post baseline visit.

Posted

Count of Participants

Participants

Baseline and every 4 weeks from baseline up to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Secondary

Proportion of Participants With a Loss ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline

The summary by visit was conducted based on the BCVA observed from each of the corresponding visit.

BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.

Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.

Every 5 letters represents 1 line of vision on the reading chart.

Posted

Count of Participants

Participants

Baseline and every 4 weeks from baseline up to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Secondary

Change From Baseline in CSFT Averaged Over Week 40 to Week 52

Change from baseline in central subfield thickness (CSFT) averaged over Week 40 to Week 52 , measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment. The number analyzed per row is the number of subjects from the FAS who had at least one CSFT assessment on scheduled visits over the corresponding time point

Posted

Mean

Standard Deviation

µm

Baseline, Week 40 to Week 52

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants

Secondary

Change From Baseline in CSFT Averaged Over Week 64 to Week 76

Change from baseline in central subfield thickness (CSFT) averaged over Week 64 to Week 76, measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment. The number analyzed per row is the number of subjects from the FAS who had at least one CSFT assessment on scheduled visits over the corresponding time point

Posted

Mean

Standard Deviation

µm

Baseline, Week 64 to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants

Secondary

Change From Baseline in CSFT by Visit up to Week 76

Change from baseline in central subfield thickness (CSFT) measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment. The number analyzed per row is the number of subjects from the FAS who had CSFT data available on baseline and the specific post-baseline visit.

Posted

Mean

Standard Deviation

µm

Baseline, and every 4 weeks from baseline up to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants

Secondary

Proportion of Subjects With Presence of Retinal Fluid (Intra- and/or Subretinal Fluid) in the Study Eye by Visit up to Week 76

Presence of retinal fluid (intra- and/or subretinal fluid) assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)

Posted

Count of Participants

Participants

Every 4 weeks from baseline up to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants

Secondary

Proportion of Subjects With a CSFT < 300 µm for the Study Eye by Visit up to Week 76

Central subfield thickness (CSFT) is measured in µm by Spectral Domain Optical Coherence Tomography (SD-OCT)

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment. The number analyzed per row is the number of subjects from the FAS who had non-missing CSFT assessment at the corresponding visit

Posted

Count of Participants

Participants

Every 4 weeks from Week 4 up to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants

Secondary

Number of Injections Between Week 24 and Week 52 and Between Week 24 and Week 72

Number of administered injections during the individualized flexible treatment (IFT) period, between Week 24 and Week 52 and between Week 24 and Week 72 are presented

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment. The number analyzed per row is the number of subjects from the FAS who were on study treatment until week 52 and until week 72.

Posted

Mean

Standard Deviation

Injections

Week 24 to Week 52 and Week 24 to Week 72

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants

Secondary

Time to Recurrence After Week 20 and up to Week 76

Recurrence is defined as the need for injection while showing a lack of disease stability for the first time after Week 20 and up to Week 76.

For subjects with recurrence after the Week 20 visit, time-to-event is calculated as (first time with the lack of disease stability - the injection date on Week 20 visit + 1). For subjects without recurrence after Week 20, the censoring time will be calculated as (last visit with disease stability assessment - the injection date on Week 20 visit + 1).

FAS-observed: The overall number of participants analyzed is the Full Analysis Set (FAS) that included all randomized subjects who received at least one intravitreal injection of the study treatment. The number analyzed is the number of subjects from the FAS who did not discontinue from study treatment on or before Week 20.

Posted

Median

95% Confidence Interval

Weeks

Week 20 to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Secondary

Number of Subjects With Ocular and Non-ocular AEs up to Week 52 and Week 76

Number of subjects with at least one ocular or non-ocular Adverse Events (AEs).

Safety Analysis Set (SAF) included all subjects who received at least one intravitreal injection.

Posted

Count of Participants

Participants

Baseline to Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Patient Reported Outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76

The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures a patient's subjective assessment of vision-related Quality of Life (QoL).

The 11 subscales in the VFQ-25 are general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated better vision-related quality of life.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 24, Week 52 and Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
OG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Secondary

Number of Subjects According to Their Anti-drug Antibody (ADA) Titer at Screening and Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76

Anti-drug antibodies (ADA) levels were assessed from subjects assigned to brolucizumab treatment only.

SAF-observed: Safety Analysis Set (SAF) included all subjects who received at least one intravitreal injection with brolucizumab. The number analyzed is the number of subjects from the SAF who had a value for ADA status on scheduled visits.

Posted

Count of Participants

Participants

Baseline, Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76

ID	Title	Description
OG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Angina pectoris	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Cardiac arrest	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Cardiac failure	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Cardiac valve disease	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Myocardial infarction	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Palpitations	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Atrial septal defect	Congenital, familial and genetic disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Cataract - Fellow eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Cataract - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0010 affected224 at risk EG0022 affected450 at risk
Glaucoma - Fellow eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Glaucoma - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Iridocyclitis - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Retinal aneurysm - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Retinal artery occlusion - Fellow eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Retinal artery occlusion - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0010 affected224 at risk EG0022 affected450 at risk
Retinal detachment - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Retinal occlusive vasculitis - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0010 affected224 at risk EG0022 affected450 at risk
Retinal vascular occlusion - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Retinal vasculitis - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0010 affected224 at risk EG0022 affected450 at risk
Uveitis - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0003 affected226 at risk EG0010 affected224 at risk EG0023 affected450 at risk
Vitreous haemorrhage - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Vitreous opacities - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Vitritis - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Mallory-Weiss syndrome	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Chest pain	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0011 affected224 at risk EG0022 affected450 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Bronchitis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0011 affected224 at risk EG0022 affected450 at risk
COVID-19	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0010 affected224 at risk EG0022 affected450 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Endophthalmitis - Study eye	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0010 affected224 at risk EG0022 affected450 at risk
Dislocation of vertebra	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Weight increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0011 affected224 at risk EG0022 affected450 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Eyelid seborrhoeic keratosis - Fellow eye	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0010 affected224 at risk EG0022 affected450 at risk
Cerebral infarction	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Syncope	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Device dislocation	Product Issues	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Depression	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Urinary retention	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Pleural mass	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk
Aortic stenosis	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected226 at risk EG0010 affected224 at risk EG0021 affected450 at risk
Vasospasm	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected226 at risk EG0011 affected224 at risk EG0021 affected450 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cataract - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0009 affected226 at risk EG0012 affected224 at risk EG00211 affected450 at risk
Conjunctival haemorrhage - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG00011 affected226 at risk EG00112 affected224 at risk EG00223 affected450 at risk
Dry eye - Fellow eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0019 affected224 at risk EG00214 affected450 at risk
Dry eye - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0006 affected226 at risk EG0019 affected224 at risk EG00215 affected450 at risk
Eye pain - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0004 affected226 at risk EG00111 affected224 at risk EG00215 affected450 at risk
Foreign body sensation in eyes - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0011 affected224 at risk EG0026 affected450 at risk
Macular oedema - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG00015 affected226 at risk EG00110 affected224 at risk EG00225 affected450 at risk
Retinal exudates - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0018 affected224 at risk EG00213 affected450 at risk
Retinal haemorrhage - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0018 affected224 at risk EG00210 affected450 at risk
Uveitis - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0010 affected224 at risk EG0025 affected450 at risk
Visual acuity reduced - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG00015 affected226 at risk EG00112 affected224 at risk EG00227 affected450 at risk
Vitreous detachment - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0015 affected224 at risk EG00210 affected450 at risk
Vitreous floaters - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG00011 affected226 at risk EG0015 affected224 at risk EG00216 affected450 at risk
Vitreous opacities - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0011 affected224 at risk EG0026 affected450 at risk
Vitritis - Study eye	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0010 affected224 at risk EG0025 affected450 at risk
Toothache	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0013 affected224 at risk EG0028 affected450 at risk
COVID-19	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0007 affected226 at risk EG0017 affected224 at risk EG00214 affected450 at risk
Nasopharyngitis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0006 affected226 at risk EG0017 affected224 at risk EG00213 affected450 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0017 affected224 at risk EG0029 affected450 at risk
Urinary tract infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0016 affected224 at risk EG00211 affected450 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0003 affected226 at risk EG0015 affected224 at risk EG0028 affected450 at risk
Intraocular pressure increased - Fellow eye	Investigations	MedDRA (24.1)	Systematic Assessment	EG0003 affected226 at risk EG0016 affected224 at risk EG0029 affected450 at risk
Intraocular pressure increased - Study eye	Investigations	MedDRA (24.1)	Systematic Assessment	EG0004 affected226 at risk EG0018 affected224 at risk EG00212 affected450 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0013 affected224 at risk EG0028 affected450 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected226 at risk EG0010 affected224 at risk EG0025 affected450 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0016 affected224 at risk EG0028 affected450 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected226 at risk EG0017 affected224 at risk EG0029 affected450 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0006 affected226 at risk EG0012 affected224 at risk EG0028 affected450 at risk
Dizziness	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0004 affected226 at risk EG0017 affected224 at risk EG00211 affected450 at risk
Hypertension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG00026 affected226 at risk EG00119 affected224 at risk EG00245 affected450 at risk

ID	Term
D012170	Retinal Vein Occlusion
D014786	Vision Disorders
D008269	Macular Edema

ID	Term
D012164	Retinal Diseases
D005128	Eye Diseases
D020246	Venous Thrombosis
D013927	Thrombosis
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D012678	Sensation Disorders
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D008268	Macular Degeneration
D012162	Retinal Degeneration

ID	Title	Description
BG000	Brolucizumab 6 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
BG001	Aflibercept 2 mg	1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Brolucizumab 6mg	Brolucizumab 6mg	0	226	32	226	109	226
EG001	Aflibercept 2mg	Aflibercept 2mg	2	224	16	224	95	224
EG002	Overall	Overall	2	450	48	450	204	450

ID	Term
C000622091	brolucizumab
C533178	aflibercept
C005703	salicylhydroxamic acid